Factors that predict development of chronic kidney disease in patients with rheumatoid arthritis receiving biologic DMARDs and mortality rates.

OBJECTIVES: We aimed to determine the choice of biologic/targeted synthetic disease-modifying anti-rheumatic drugs (b/ts-DMARDs), factors associated with the development of chronic kidney disease (CKD), and mortality in RA patients with CKD receiving b/ts-DMARDs. METHODS: Two thousand one hundred forty-one RA (79.4% female) patients were included in the analysis from the HUR-BIO prospective registry. Patients were divided into the CKD group and the non-CKD group. Age and gender-matched patients were selected from the non-CKD group, and then three main groups were determined. CKD was staged according to the glomerular filtration rate criteria. The clinical characteristics of the patients, disease activities, treatment choices, drug retention rate, and mortality rates were compared between the groups. RESULTS: CKD was detected in 90/2141 (4.2%) RA patients on b/ts-DMARDs. Forty patients (2.3%) developed CKD during follow-up after the initiation of b/ts-DMARDs. In the CKD group, anti-TNF agents were chosen as the first-line b/ts-DMARDs therapy in 64.4% of patients, with etanercept leading in 31 (34.4%) patients. In multivariate analysis, age at the start of treatment, DAS-28-ESR at last visit, amyloidosis, hypertension, and history of smoking were the factors associated with the development of CKD in RA patients receiving b/ts-DMARDs. The mortality rate in RA-CKD patients until the onset of the pandemic was 15.41 per 1000 patient years, whereas it was 85.9 per 1000 patient years after the pandemic. CONCLUSION: Comorbidities and control of disease activity are critical in the development of CKD in RA patients receiving b/ts-DMARDs. While there was no significant difference in mortality rate between CKD and non-CKD patients, the overall mortality rate increased after the COVID-19 pandemic duration in both groups.

Immunotherapy in the First-Line Treatment of Advanced Nasopharyngeal Carcinoma: A Systematic Review and Meta-Analysis.

OBJECTIVES: Data regarding the clinical benefits of immune checkpoint inhibitors (ICIs) are limited in nasopharyngeal carcinoma (NPC). Therefore, we conducted a meta-analysis of phase-III clinical trials to evaluate the benefit of adding ICIs to chemotherapy in the first-line treatment of advanced NPC. METHODS: We conducted a systematic review using Web of Science, PubMed, and Embase for studies published until September 21, 2022. The meta-analyses were performed with the generic inverse-variance method with a random-effects model. Hazard ratios (HRs) with 95% confidence interval (CI) for progression-free survival (PFS) and overall survival (OS) were the principal summary measures. This protocol was registered in the PROSPERO database (registration number: CRD 42022361866). RESULTS: Three eligible studies with a total of 815 patients were included. The addition of ICIs to standard chemotherapy significantly improved PFS (HR: 0.52, 95% CI: 0.43-0.63, p < 0.0001). Although the OS results were immature, ICIs significantly reduced the risk of death (HR: 0.63, 95% CI: 0.47-0.84, p = 0.0020). The benefit of ICIs was consistent regardless of initial disease presentation (recurrent or de novo), baseline EBV levels, PD-L1 expression, and ECOG performance status. No significant difference in the rates of serious adverse events (HR = 0.98, 95% CI 0.74-1.30) was found between the two groups. CONCLUSION: The available evidence demonstrates that adding ICIs to chemotherapy in the first-line treatment of advanced NPC provided better PFS with acceptable safety. However, a longer follow-up is required to evaluate the true OS benefit of these combinations. LEVEL OF EVIDENCE: NA Laryngoscope, 134:7-17, 2024.

Seven-Year Single-Center Experience of the Efficacy and Safety of Ferric Carboxymaltose in Cancer Patients with Iron-Deficiency Anemia.

Anemia remains an essential concern affecting the quality of life and the survival of cancer patients. Although there are different approaches to treating anemia in cancer patients, the number of studies reporting the efficacy of iron replacement in cancer patients is limited. In this study, the efficacy and safety of iron carboxymaltose, a parenteral iron treatment option, in the treatment of anemia, were examined retrospectively. A total of 1102 adult patients who received IV ferric carboxymaltose treatment at Hacettepe Oncology Hospital between 2014 and 2020 were included. The mean hemoglobin change observed at the end of the 12th week was 1.8 g/dL, and the rate of patients with an increase in hemoglobin of 1 g/dL or more was 72.1%. It was observed that the treatment demonstrated effectiveness in patients receiving active cancer treatment in all tumor types. The treatment was generally safe, and no grade 3-5 side effects were observed in the patients included in the study. According to one of the most extensive series published in the literature, iron carboxymaltose is an efficient and safe alternative for cancer patients with iron-deficiency anemia.

Isolation and characterization of yogurt starter cultures from traditional yogurts and growth kinetics of selected cultures under lab-scale fermentation.

The development of new starter cultures is a crucial task for the food industry to meet technological requirements and traditional products are important reservoirs for new starter cultures. In this respect, this study aimed to isolate, identify, and determine the technological characteristics of Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus strains originated from traditional yogurt samples. Genotypic discrimination of 200 isolates revealed the presence of distinct 19 S. thermophilus and 11 Lb. delbrueckii subsp. bulgaricus strains as potential starter cultures. Strain-specific properties determined the acidification capacity of the yogurt starter cultures and a higher acidification capacity was observed for S. thermophilus strains compared to Lb. delbrueckii subsp. bulgaricus strains. Proteolytic activity was found between 0.012-0.172 and 0.078-0.406 for S. thermophilus and Lb. delbrueckii subsp. bulgaricus strains, respectively. 4 of S. thermophilus and 3 of Lb. delbrueckii subsp. bulgaricus strains were found resistant to all tested bacteriophages. The antibiotic susceptibility tests of the isolates revealed that a very low antibiotic resistance was observed for the yogurt starter cultures. Finally, the growth kinetics of selected strains were determined and the maximum specific growth rate of selected S. thermophilus and Lb. delbrueckii subsp. bulgaricus was calculated as 0.527 h-1 and 0.589 h-1, respectively.

Genetic diversity and population structure of Saccharomyces cerevisiae isolated from Turkish sourdough by iPBS-retrotransposons markers.

Molecular DNA markers are valuable tools for analyzing genetic variation among yeast from different populations to reveal the genetically different autochthonous strains. In this study, we employed inter-primer binding site (iPBS) retrotransposon polymorphism to assess the genetic variation and population structure of 96 Saccharomyces cerevisiae isolates from four different regions in Turkey. The nine selected iPBS primers amplified 102 reproducible and scorable bands, of which 95.10% were polymorphic with an average of 10.78 polymorphic fragments per primer. The average polymorphism information content and the resolving power were 0.26-3.58, respectively. Analysis of molecular variance (AMOVA) revealed significant (P < 0.001) genetic differences within populations (88%) and between populations (12%). The unweighted pair group mean with arithmetic (UPGMA) dendrogram grouped 96 S. cerevisiae strains into two main clusters, where the highest probability of the data elucidating the population structure was obtained at ΔK = 2. There was not an obvious genetic discrimination of the populations according to geographical regions on UPGMA, supported by principal coordinate analysis. However, the individuals of the closer provinces in each population were more likely to group together or closely. The results indicate that iPBS polymorphism is a useful tool to reveal the genetically diverse autochthonous S. cerevisiae strains that may be important for the production of sourdough or baked goods.

The use of fulvestrant before chemotherapy improves survival in hormone-positive breast cancer: a real-life study.

BACKGROUND: We aimed to evaluate the efficacy of fulvestrant and its affecting clinical factors, including the optimal sequencing of fulvestrant and chemotherapy in a real-life cohort. METHODS: The data of 256 metastatic hormone-positive breast cancer patients treated with fulvestrant were evaluated. The association of clinical factors with survival was analyzed with Kaplan-Meier and Cox-regression analyses. RESULTS: The median age of patients was 57 years. More than half of the patients used fulvestrant in later lines and after chemotherapy (75.8%). The median progression-free (PFS) and overall survival (OS) of all cohort were 6.05 ± 0.56 and 29.70 ± 1.61 months, respectively. Primary endocrine resistance (HR: 1.989, 95% CI: 1.430-2.766, <0.001), use of fulvestrant after chemotherapy (HR: 1.849, 95% CI: 1.182-2.891, p = 0.007) and visceral metastases (HR: 1.587, 95% CI: 1.128-2.233, p = 0.008) were associated with decreased OS in multivariate analyses. Sixteen patients were treated with trastuzumab and fulvestrant combination. The overall response rate (p = 0.340), disease control rate (p = 0.076), and OS (p = 0.289) and PFS (p = 0.276) were similar to overall cohort. DISCUSSION: In our experience, fulvestrant treatment was associated with comparable OS to clinical trials in a large cohort of patients. Patients treated with fulvestrant before chemotherapy were garnered significantly more benefit.

Start Codon Targeted (SCoT) markers for the assessment of genetic diversity in yeast isolated from Turkish sourdough.

Molecular markers are valuable tools for assessing the genetic variation in yeast. Here, we investigated the utility of SCoT markers for the genetic characterization of yeast strains at inter and intraspecies levels. A total of 345 endogenous yeast strains were isolated from 65 Type I sourdough samples collected from six different regions of Turkey. The seven SCoT primers produced 221 bands, of which 95.47% were polymorphic. Each primer could successfully differentiate species, supported by PIC and RP values. The ITS sequencing of isolates selected from the UPGMA dendrogram revealed that Saccharomyces cerevisiae predominated the microflora, followed by Kazachstania servazzii, K. humilis, Wickerhamomyces anomalus, Torulaspora delbrueckii, and Pichia kudriavzevii, respectively. The AMOVA revealed a high genetic variation between (49%) and within populations (51%) for S. cerevisiae. The high gene flow observed among S. cerevisiae populations suggests that it may have contributed to the geographical evolution of S. cerevisiae via the transportation of the sourdough samples. The different geographical origins were most likely to group separately on the UPGMA and PCoA. Saccharomyces cerevisiae strains from more distant populations generally displayed more significant genetic variation. SCoT markers can successfully be used alone or with the other existing DNA markers for DNA fingerprinting and analyzing the genetic variation between and within species.

The Association between Early Changes in Neutrophil-Lymphocyte Ratio and Survival in Patients Treated with Immunotherapy.

Dynamic changes in the blood-based biomarkers could be used as a prognostic biomarker in patients treated with immune checkpoint inhibitors (ICIs), although the data are limited. We evaluated the association between the neutrophil−lymphocyte ratio (NLR) and early NLR changes with survival in ICI-treated patients. We retrospectively evaluated the data of 231 patients with advanced-stage cancer. We recorded baseline clinical characteristics, baseline NLR and fourth-week NLR changes, and survival data. A compound prognostic score, the NLR2-CEL score, was developed with the following parameters: baseline NLR (<5 vs. ≥5), ECOG status (0 vs. ≥1), Charlson Comorbidity Index (CCI, <9 vs. ≥9), LDH (N vs. ≥ULN), and fourth-week NLR change (10% or over NLR increase). In the multivariable analyses, higher NLR (HR: 1.743, p = 0.002), 10% or over NLR increase in the fourth week of treatment (HR: 1.807, p = 0.001), higher ECOG performance score (HR: 1.552, p = 0.006), higher LDH levels (HR: 1.454, p = 0.017), and higher CCI (HR: 1.400, p = 0.041) were associated with decreased OS. Compared to patients with the lowest scores, patients in the highest score group had significantly lower OS (HR: 7.967, 95% CI: 3.531−17.979, p < 0.001) and PFS. The composite score had moderate success for survival prediction, with an AUC of 0.702 (95% CI: 0.626−0.779, p < 0.001). We observed significantly lower survival in patients with higher baseline NLR values and increased NLR values under treatment.

The efficacy of immune checkpoint inhibitors in rare tumors: A systematic review of published clinical trials.

The immune checkpoint inhibitors (ICIs) entered treatment algorithms in most tumors. However, the data on the efficacy is limited in rare tumors with no phase III studies. We systemically reviewed the clinical trials evaluating the ICI efficacy in rare tumors and included a total of 47 clinical trials in this review. The ICIs demonstrated over 30% response rates in Merkel cell carcinoma and squamous cell carcinoma of the skin and became the standard of care. Additionally, the ICI efficacy was promising in thymic epithelial tumors and gestational trophoblastic neoplasia. In contrast, the ICI efficacy is limited in most sarcomas, germ cell tumors and low-grade neuroendocrine tumors. The ICI efficacy seemed to be improved with combinations targeting tumor microenvironment in sarcomas. The available evidence on ICI efficacy in rare tumors denote a need for better patient selection and novel combination strategies to improve outcomes.

The association between albumin-globulin ratio (AGR) and survival in patients treated with immune checkpoint inhibitors.

BACKGROUND: The albumin-globulin ratio (AGR) could be a prognostic biomarker in patients with cancer, although the data is limited in patients treated with immune-checkpoint inhibitors (ICIs). OBJECTIVES: We aimed to evaluate the association between AGR and survival in ICI-treated patients. METHODS: The data of 212 advanced-stage patients were retrospectively evaluated in this cohort study. The association between AGR with overall (OS) and progression-free survival (PFS) were evaluated with multivariate analyses. Additionally, receptor operating curve (ROC) analysis was conducted to assess the AGR's predictive power in the very early progression (progression within two months) and long-term benefit (more than twelve months survival). RESULTS: The median AGR was calculated as 1.21, and patients were classified into AGR-low and high subgroups according to the median. In the multivariate analyses, patients with lower AGR (< 1.21) had decreased OS (HR: 1.530, 95% CI: 1.100-2.127, p= 0.011) and PFS (HR: 1.390, 95% CI: 1.020-1.895, p= 0.037). The area under curve of AGR to detect early progression and long-term benefit were 0.654 (95% CI: 0.562-0.747, p= 0.001) and 0.671 (95% CI: 0.598-0.744, p< 0.001), respectively. CONCLUSIONS: In our experience, survival with ICIs was impaired in patients with lower AGR. Additionally, the AGR values could detect the very early progression and long-term benefit ICIs.

The use of fulvestrant before chemotherapy improves survival in hormone-positive breast cancer: a real-life study.

BACKGROUND/AIM: We aimed to evaluate the efficacy of fulvestrant and affecting clinical factors, including the optimal sequencing of fulvestrant and chemotherapy in a real-life cohort. METHODS: The data of 256 metastatic hormone-positive breast cancer patients treated with fulvestrant were evaluated. The association of clinical factors with survival was analyzed with Kaplan-Meier and Cox-regression analyses. RESULTS: The median age of patients was 57 years. More than half of the patients used fulvestrant in later lines and after chemotherapy (75.8%). The median progression-free (PFS) and overall survival (OS) of all cohort were 6.05+/-0.56 and 29.70+/-1.61 months, respectively. Primary endocrine resistance (HR: 1.989, 95% CI: 1.430-2.766, <0.001), use of fulvestrant after chemotherapy (HR: 1.849, 95% CI: 1.182-2.891, p=0.007) and visceral metastases (HR: 1.587, 95% CI: 1.128-2.233, p=0.008) were associated with decreased OS in multivariate analyses. Sixteen patients were treated with trastuzumab and fulvestrant combination. The overall response rate (p=0.340), disease control rate (p=0.076), and OS (p=0.289) and PFS (p=0.276) were similar to overall cohort. CONCLUSION: In our experience, fulvestrant treatment was associated with comparable OS to clinical trials in a large cohort of patients. Patients treated with fulvestrant before chemotherapy were garnered significantly more benefit.

The association of BMI and sarcopenia with survival in patients with glioblastoma multiforme.

Background: The association between obesity and sarcopenia (via temporal muscle thickness) with overall survival (OS) has been evaluated in several glioblastoma multiforme studies, however, the data are inconclusive. Methods: The authors conducted meta-analyses via the generic inverse-variance method with a random-effects model. Results: In the pooled analysis of five studies, including 973 patients, patients with lower temporal muscle thickness had significantly decreased OS (HR: 1.62, 95% CI: 1.16-2.28, p = 0.005). The pooled analysis of five studies, including 2131 patients, demonstrated decreased OS in patients with lower BMI compared with patients with obesity (HR: 1.45, 95% CI: 1.12-1.88, p = 0.005). Conclusion: Readily available body composition parameters could be used for prognosis prediction and to aid in treatment decisions in patients with glioblastoma multiforme.

Evaluation of early unplanned readmissions and predisposing factors in an oncology clinic.

BACKGROUND: Unplanned readmission in the first 30 days after discharge is an important medical problem, although the data on cancer patients is limited. So we planned to evaluate the rates and causes of early readmissions and the predisposing factors. METHODS: Patients hospitalized in Hacettepe University Oncology services between August 2018 and July 2019 were included. The demographic features, tumor stages, regular drugs, last laboratory parameters before discharge, and readmissions in the first 30 days after discharge were recorded. The predisposing features were evaluated with univariate and multivariate analyses. RESULTS: A total of 562 hospitalizations were included. The mean age of the patients was 58.5 ± 14.5 years. Almost 2/3 of the hospitalizations were due to symptom palliation and infections. Eighty-three percent of the patients had advanced disease, and over 60% had an ECOG score of 2 and above. In the first 30 days after discharge, 127 patients were readmitted (22.6%). Advanced stage disease, presence of polypharmacy (5 or more regular drugs), hospitalization setting (emergency department (ED) vs. outpatient clinic), and hypoalbuminemia (< 3 gr/dL) were associated with a statistically significant increase in the risk of readmission. Among these factors, advanced-stage disease (HR: 2.847, 95% CI: 1.375-5.895), hospitalization from ED (HR: 1.832, 95% CI: 1.208-2.777), and polypharmacy (HR: 1.782, 95% CI: 1.173-2.706) remained significant in multivariate analyses. CONCLUSIONS: In this study, 22% of cancer patients had early readmissions. The readmission risk increased in patients with advanced disease, hospitalization from ED, and polypharmacy. The optimal post-discharge plan may reduce readmissions in all oncology patients, with priority for these patient groups.

The utility of iPBS retrotransposons markers to analyze genetic variation in yeast.

Yeasts are one of the main organisms in the food industry and effective components of many ecosystems. The method for identifying and detecting certain yeast species or strains is a crucial step for the food industry and should be simple, reliable, fast, and inexpensive. In our study, inter-priming binding sites (iPBS) retrotransposon marker system was employed to elucidate the genetic variability at intraspecies and interspecies levels among 112 yeast strains belonging to eight species previously obtained from fermented foods. The molecular identification of yeast strains was firstly confirmed by sequencing the D1/D2 domain of the 26S rRNA. The eight selected retrotransposon-based primers produced 278 bands, all of which were polymorphic with an average of 34.75 polymorphic fragments per primer. The averages of polymorphism information contents and the resolving power values for the iPBS marker system were 0.23 and 10.11, respectively. The genetic parameters within each yeast species obtained from iPBS markers were observed as; the percentage of polymorphic loci for each species ranging from 19.23% to 71.21%, Nei's gene diversity from 0.085 to 0.228, while Shannon's information index values ranging from 0.125 to 0.349. The value of gene flow (0.09) and genetic variation among the populations (0.85) showed higher genetic variation among the species. UPGMA analyses demonstrated considerable genetic variability in the yeast strains, clustered them according to their species, and revealed the intraspecific variation. Each of the selected iPBS primer provided enough species-discrimination. Present evaluations suggest the utility of iPBS marker system to estimate the genetic variation of yeast strains. This study is a preliminary point for further studies on the identification methodology, and population genetics of yeast species having importance in the food industry with iPBS markers.

Microencapsulation of phages to analyze their demeanor in physiological conditions.

Nowadays, phage therapy emerges as one of the alternative solutions to the problems arising from antibiotic resistance in pathogenic bacteria. Although phage therapy has been successfully applied both in vitro and in vivo, one of the biggest concerns in this regard is the stability of phages in body environment. Within the scope of this study, microencapsulation technology was used to increase the resistance of phages to physiological conditions, and the resulting microcapsules were tested in environments simulating body conditions. For this purpose, Bacillus subtilis, Salmonella enterica subsp. enterica serovar Enteritidis (Salmonella Enteritidis), and Salmonella enterica subsp. enterica serovar Typhimurium (Salmonella Typhimurium) phages were isolated from different sources and then microencapsulated with 1.33% (w/v) sodium alginate using a spray dryer to minimize the damage of physiological environment. Stability of microcapsules in simulated gastric fluid and bile salt presence was tested. As a consequence, the maximum titer decrease of microencapsulated phages after 2-h incubation was found to be 2.29 log unit for B. subtilis phages, 1.71 log unit for S. Enteritidis phages, and 0.60 log unit for S. Typhimurium phages, while free phages lost their viability even after a 15-min incubation. Similarly, microencapsulation was found to increase the stability of phages in the bile salt medium and it was seen that after 3 h of incubation, the difference between the titers of microencapsulated phages and free phages could reach up to 3 log unit.

Technological properties of indigenous wine yeast strains isolated from wine production regions of Turkey.

The purpose of this study was to evaluate the important technological and fermentative properties of wine yeast strains previously isolated from different wine producing regions of Turkey. The determination of the following important properties was made: growth at high temperatures; fermentative capability in the presence of high sugar concentration; fermentation rate; hydrogen sulfide production; killer activity; resistance to high ethanol and sulfur dioxide; foam production; and enzymatic profiles. Ten local wine yeast strains belonging to Saccharomyces, and one commercial active dry yeast as a reference strain were evaluated. Fermentation characteristics were evaluated in terms of kinetic parameters, including ethanol yield (YP/S), biomass yield (YX/S), theoretical ethanol yield (%), specific ethanol production rate (qp; g/gh), specific glucose uptake rate (qs; g/gh), and the substrate conversion (%). All tested strains were able to grow at 37 °C and to start fermentation at 30° Brix, and were resistant to high concentrations of sulfur dioxide. 60 % of the strains were weak H2S producers, while the others produced high levels. Foam production was high, and no strains had killer activity. Six of the tested strains had the ability to grow and ferment at concentrations of 14 % ethanol. Except for one strain, all fermented most of the media sugars at a high rate, producing 11.0-12.4 % (v/v) ethanol. Although all but one strain had suitable characteristics for wine production, they possessed poor activities of glycosidase, esterase and proteinase enzymes of oenological interest. Nine of the ten local yeast strains were selected for their good oenological properties and their suitability as a wine starter culture.

Evaluation of increased incubation temperature and cefixime-tellurite treatment for the isolation of Escherichia coli O157:H7 from minced beef.

To improve enrichment and isolation of Escherichia coli O157:H7, this study evaluated increased incubation temperature and cefixime-tellurite (CT) on five strains of each of the following bacteria, E. coli, Hafnia alvei, Enterobacter spp., Citrobacter freundii and E. coli O157:H7, and two strains of E. coli O157:nH7. These were grown in pure culture in LST broth with varying cefixime-tellurite concentrations. A range of incubation temperatures from 37 to 46 degrees C was investigated for the inhibition of cohabitant microorganisms. Minced beef, spiked with E. coli O157:H7 and cohabitant microorganisms was investigated. Increased incubation temperature (42 degrees C) and treatment with half of the prescribed amount of cefixime-tellurite by BAM for SMAC agar in enrichment step were the most effective in selectively growing E. coli O157:H7. The results show that E. coli O157:H7 is more resistant to these two conditions than the other cohabitant bacteria.